The IL12 Receptor Beta 1 (IL12Rβ1) gene is transcribed in two isoforms by human peripheral blood-derived dendritic cells (HPBDC) when exposed to Mycobacterium tuberculosis (Robinson et al. J. Exp. Med. 2010. 207:591-605). Absence of IL-12Rβ1 function predisposes humans to increased susceptibility to tuberculosis (de Beaucoudrey et al, Medicine 2010. 89: 381-402), but no function has been ascribed to the alternative splice variant (IL12Rβ1 isoform 2), which is induced strongly by M. tuberculosis. Since IL12Rβ1 is known to mediate the activity of the cytokines including IL-12p70, IL-23 and IL-12(p40)2 it has the potential to impact many aspects of the immune response. These cytokines are involved in the regulation of damaging inflammatory responses associated with chronic diseases and are also of interest to researchers studying protective immunity to pathogens.
Tuberculosis (TB) is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria. The main cause of tuberculosis is M. tuberculosis, a small, aerobic, nonmotile bacillus. Tuberculosis typically attacks the lungs, but can also affect other parts of the body. It is spread through the air when people who have an active tuberculosis infection cough, sneeze, or otherwise transmit their saliva through the air. About 90% of those infected have asymptomatic, latent tuberculosis infections, with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculosis. However, latent infections that progresses to active disease kill more than 50% of individuals if untreated. Diagnosis of active tuberculosis relies on radiology (commonly chest X-rays), as well as microscopic examination and microbiological culture of body fluids. Diagnosis of latent tuberculosis relies on the tuberculin skin test (TST) and/or blood tests. Treatment is difficult and requires administration of multiple antibiotics over a long period of time. A definitive diagnosis of tuberculosis is made by identifying M. tuberculosis in a clinical sample (e.g. sputum, pus, or a tissue biopsy). However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture.
There is a need to differentiate between people who are infected with M. tuberculosis but not developing disease from those that do have or are on the way to developing disease. It is also important to determine when people are responding to treatment.